Recently, in the field of pharmaceuticals and diagnostic agents, large amounts of highly specific antibodies are needed for treatment and diagnosis of diseases. Antibodies are usually produced using mammals such as mice, rats, and rabbits, but they have recently been produced using cells of microorganisms or mammals, transgenic animals, transgenic plants and such. Characteristics of recombinant antibodies are that they can be produced at the same quality in large amounts and they are safe since viral diseases and the like are not incorporated and such; therefore, they are expected to become more important in the future.
On the other hand, recombinant antibodies also have many problems. For example, in microorganisms such as E. coli, only part of an antibody is produced and since glycosylation and phosphorylation of produced antibodies are insufficient, they are not sufficiently suitable for use as pharmaceuticals or diagnostic agents. Furthermore, human antibodies are generally known to be insoluble when produced by E. coli and such. Accordingly, purification of such antibodies requires the steps of solubilizing proteins with denaturants such as SDS and recovering activities of the proteins by gradually removing the denaturants in solution by dialysis or such.
Furthermore, when mammalian cells are used, production cost increases and thus large-scale production is difficult. Therefore, antibody production using transgenic animals and plants has been attempted, but it is still being studied. When other eukaryotic cells are used, a special signal is necessary to secrete an antibody out of the cells.
Silkworms have an organ called the silk gland, and a single silkworm has the ability to produce a maximum of 0.5 g of protein. In recent years, production techniques of transgenic silkworms have been developed, and methods for introducing foreign genes and for regulating expression of transgenes have advanced. Thus, it has now become possible to express transgenes in the silk gland and produce recombinant proteins. Since silkworms are eukaryotes, they can produce proteins similar to mammalian proteins compared to plants or microorganisms such as E. coli. In addition, silkworms can be reared on an artificial diet under clean conditions, and large-scale rearing at the level of several tens of thousands of silkworms can be easily carried out.    [Patent Document 1] Japanese Patent Application Kokai Publication No. (JP-A) 2006-137739: Tamura T. et al. “Method of protein production using a silkworm middle silk gland-specific gene expression system”, filed by National Institute of Agrobiological Sciences on Mar. 15, 2005    [Non-patent Document 1] Tamura T., Sezutsu H., Kobayashi I., Kojima K., Kanda T., and Uchino K. (1999) “Methods for producing transformed silkworms using a transposon” Abstracts of the 7th Workshop on Insect Function, p. 10-22    [Non-patent Document 2] Tamura, T., Thibert, C., Royer, C., Kanda, T., Abraham, E., Kamba, M., Komoto, N., Thomas, J.-L., Mauchamp, B., Chavancy, G., Shirk, P., Fraser, M., Prudhomme, J.-C., and Couble, P. (2000) “A piggyBac element-derived vector efficiently promotes germ-line transformation in the silkworm Bombyx mori L.” Nature Biotechnology 18, 81-84    [Non-patent Document 3] Tomita M, M. H., Sato T, Adachi T, Hino R, Hayashi M, Shimizu K, Nakamura N, Tamura T, Yoshizato K. (2003) “Transgenic silkworms produce recombinant human type III procollagen in cocoons.” Nat Biotechnol 21, 52-56    [Non-patent Document 4] Tamura T. (2000) “Transgenic silkworms: Current status and prospects” J. Sericul. Sci. Japan, 69, 1-12    [Non-patent Document 5] Tamura T. (2000) “Introduction of useful genes in silkworm development” Reports of the 21st Symposium on Basic Breeding: Advancement of developmental engineering in molecular breeding of animals and plants, p. 23-29    [Non-patent Document 6] Tamura, T., Quan, G. X., Kanda, T., and Kuwabara, N. (2001) “Transgenic silkworm research in Japan: Recent progress and future” Proceeding of Joint International Symposium of Insect COE Research Program and Insect Factory Research Project. p. 77-82    [Non-patent Document 7] Imamma, M., Nakai, J., Inoue, S., Quan, G-X., Kanda T., and Tamura, T. (2003) “Targeted gene expression using the Gal4/UAS system in the silkworm Bombyx mori.” Genetics, 165, 1329-1340    [Non-patent Document 8] Tamura, T. (2004) “Development and prospect of a production system for useful substances using transgenic silkworms” Bio Industry 20(3), 28-35    [Non-patent Document 9] Tamura, T., Uchino, K., Kanda, T., Kobayashi, I., and Kojima, K. (2004) “Production of a middle silk gland-specific gene expression system that uses the yeast GAL4/UAS system” Abstracts of the Meeting of the Japanese Society of Sericultural Science 74, p. 51    [Non-patent Document 10] Tamura T. (2004) “Establishment of methods for producing transgenic silkworms—expected to be applied to production of fibers with novel functions” Kagaku to Seibutsu (Chemistry and Biology) 42, 634-635    [Non-patent Document 11] Tamura, T. (2004) “Production of transgenic silkworms and useful substances” Biologics: Development of products using biological substances (The Society of Polymer Science, ed.) pp. 45-68.    [Non-patent Document 12] Ueda, K. (2004) “The forefront of antibody engineering” p. 122. CMC Publishing, Tokyo.    [Non-patent Document 13] Kiyokawa, I., Kobayashi, I., Uchino, K., Sezutsu, H., Kanda, T., Tamura, T., Miura, T., Ohashi, T., and Katayama K. (2006) “Production of hexokinase and anti-human transferrin antibody for clinical diagnostic reagent using transgenic silkworm” Abstracts of the 7th International Workshop on the Molecular Biology and Genetics of the Lepidoptera, p 94